This invention relates to a method of reducing insulin resistance in humans in whom Impaired Glucose Tolerance (IGT) and Non-Insulin Dependent Diabetes Mellitus (NIDDM) have not presented.
At present, a person who has a fasting plasma glucose level of greater than 7.8 mmol/l is classified as being diabetic (although this value is currently under review and may soon be set at a lower level, between 6 and 7 mmol/l). However, there is a standard means of classifying whether or not a person is diabetic, and this is important when a person has a fasting blood glucose level just below the above stated level. This means is called the Oral Glucose Tolerance Test (OGTT).
The OGTT is conducted in the following manner. After an overnight fast of 10-16 hours, a fasting blood glucose reading is taken. Glucose (75 g) is administered orally in water (250-300 ml). A further blood glucose reading is taken after 2 hours. Diabetes is diagnosed if the fasting glucose level is greater than 7.8 mmol/l or if the 2 hour level is greater than 11.1 mmol/l. Impaired Glucose Tolerance (IGT) is diagnosed if the fasting glucose level is less than 7.8 mmol/l and the 2 hour value is in the range 7.8-11.1 mmol/l. Normal glucose tolerance is declared if both the fasting glucose level and the 2 hour level are less than 7.8 mmol/l.
The majority of people are non-diabetic and have normal glucose tolerance. A proportion of these people will be at risk of developing Impaired Glucose Tolerance and/or diabetes in the future. One well-documented risk-factor is obesity, in which mild insulin resistance is a common phenomenon. This is often compensated for in the obese body by an increase in the plasma insulin level. However, the body can only increase its insulin secretion to a certain level, so if the insulin resistance continues to worsen in an obese person, eventually the body will not be able to compensate by providing extra insulin. At this time the plasma glucose levels will start to become elevated, presenting IGT or Non-Insulin Dependent Diabetes Mellitus (NIDDM).
Clearly, this gradual decline towards IGT and NIDDM is undesirable both for the individual and in terms of the cost of healthcare. It would, therefore, be advantageous to restrict insulin resistance for as long as possible in these people.
The term xe2x80x9cglucose tolerancexe2x80x9d includes glucose disposal in muscle tissue, and hepatic glucose output.
The term xe2x80x9cInsulin resistancexe2x80x9d means a reduced biological response to insulin. Insulin resistance can involve effects on both hepatic glucose output and peripheral glucose uptake, and may be due to reduced insulin receptor numbers, reduced tyrosine kinase activity of the insulin receptor and/or abnormalities distal to the receptor.
Surprisingly, it has now been found that the administration of certain arylcyclobutylalkylamines has efficacy in reducing insulin resistance.